CANCER AND STEM CELL BIOLOGY RESEARCH PROGRAM (CSCB) ABSTRACT The Cancer and Stem Cell Biology Research Program (CSCB) is led by Director Gay Crooks, MBBS, who specializes in hematopoietic stem/progenitor cell transplantation and Co-Director Brigitte Gomperts, MD, who studies lung carcinogenesis and the role of the microenvironment. CSCB links basic and translational investigators studying biological processes shared between stem cells and malignancy. Program members expect that a detailed understanding of the mechanisms of normal and aberrant cell self-renewal and differentiation will reveal novel biological insights into cancer initiation, progression, and recurrence, thereby enabling exploration of novel therapeutic targets and biomarkers. CSCB basic, translational, and clinical researchers study normal stem cells and their malignant counterparts originating from two biological sources, hematopoiesis and epithelia. Scientific interactions between the two tissue platforms integrate by sharing common conceptual frameworks and experimental tools. The Program objective is to understand the intrinsic and extrinsic mechanisms that control homeostasis in healthy tissues that go awry in malignancy, and to harness these mechanisms for cancer treatment. Three specific aims guide achieving the Program objective. Aim 1- To understand how the biology of epithelial stem cells is regulated during malignant transformation and normal development. Aim 2- To define the mechanisms that regulate growth and differentiation of hematopoietic stem and progenitor cells during malignant transformation, normal development, and after transplantation. Aim 3- To determine the role of the microenvironment in tumor formation and stem cell regulation. The CSCB program has 36 faculty from 16 departments spanning four UCLA schools and affiliated institution Caltech, that together provide the breadth and depth of expertise needed to achieve scientific and programmatic goals. Program members are highly productive and collaborative with 633 cancer publications during the prior project period, 31% of which are inter-programmatic, 6% of which are intra-programmatic, and 44% of which are in high-impact (IF ?10, or field leading) journals. Members have support from $11,389,786 in cancer funding, of which $2.7M (23%) is from the NCI and $8.1M (71%) is peer-reviewed. Program science is highly dependent on the JCCC, with significant member use of all six Shared Resources, the Seed and Impact grant programs, space allocations, and recruitment and retention of key investigators. Each CSCB investigator has a dominant interest in either hematopoietic or epithelial stem cells, although the shared biology of stem cells and cancer in all tissue types has led to an immensely fertile and interactive Program environment across platforms. These interactions benefit from a close collaboration between the JCCC and the UCLA Broad Stem Cell Research Center (BSCRC) over the past 12 years. Almost every investigator in CSCB works on at least two of the three specific aims, using combinations of animal model systems, human pluripotent stem cells, and primary human tissues to uncover basic biologic processes and reveal new opportunities for cancer treatment.